Although the prevalence of chronic obstructive pulmonary disease (COPD) is not known, it is estimated that approximately 14 million persons in the United States suffer from the condition, with the estimated number having increased some 42% between 1982 and 1995. Estimates of COPD in population-based studies in the United States range between 4% to 6% of adult white males and from 1% to 3% of adult white females.
In 1991, there were 85,444 deaths due to COPD and allied conditions, a death rate of 18.6 per 100,000 persons, ranking the condition as the fourth leading cause of death in the United States.
In the past, therapeutic methods for the treatment of COPD included the administration, typically by means of a metered dose inhaler (MDI), of a sympathomimetic bronchodilator such as ephedrine, epinephrine, or isoproterenol. The use of these agents, however, has been replaced more recently by more .beta..sub.2 -specific bronchodilators such as metaproterenol, albuterol, terbutaline, and bitolterol, generally administered as aerosols.
Oral sustained-release formulations of theophylline are generally given for chronic maintenance therapy. Although the benefits of theophylline treatment in patients with COPD are generally difficult to prove, this form of treatment remains popular.
Anticholinergics such as atropine sulfate and ipratroprium, a quaternary ammonium derivative of atropine, have been used for the inhalation treatment of COPD, although the former is not approved for use. Because of its quaternary ammonium salt nature, ipratroprium is minimally absorbed into the blood stream and has fewer side effects than atropine.
Inhaled corticosteroids are often effective for mild to moderate asthmatics, whereas such use has been shown to be efficacious in only a small percentage of COPD patients.
Because of the wide prevalence of chronic obstructive pulmonary disease, and its high ranking among the leading causes of death, there is a continuing need for the discovery and development of new agents for the treatment and amelioration of the disease.
U.S. Pat. No. 5,180,742 and its division, U.S. Pat. No. 5,304,658, both to Terao, et al., disclose a class of quinone derivatives for use in the inhibition of lipid peroxidase activity, as antagonists of thromboxane A.sub.2 receptors, or as inhibitors of the activity of 5-lipoxygenase activity.
U.S. Pat. No. 5,534,548 to Killian discloses the use of a class of substituted (.OMEGA.-1,4-benzoquinon-2-yl)-alkanoic acids for the treatment or prevention of eclampsia or preeclampsia in pregnant women.